TY - JOUR
T1 - Synthesis, Radiolabeling, and in Vitro and in Vivo Evaluation of [ 18 F]ENL30
T2 - A Potential PET Radiotracer for the 5-HT 7 Receptor
AU - Tampio L'Estrade, Elina
AU - Edgar, Fraser G.
AU - Xiong, Mengfei
AU - Shalgunov, Vladimir
AU - Baerentzen, Simone L.
AU - Erlandsson, Maria
AU - Ohlsson, Tomas G.
AU - Palner, Mikael
AU - Knudsen, Gitte M.
AU - Herth, Matthias M.
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/4/23
Y1 - 2019/4/23
N2 - The 5-HT 7 receptor (5-HT 7 R) is involved in a broad range of physiological conditions and disorders. Currently, there is no validated clinical positron emission tomography (PET) tracer available; however, we have recently developed a promising 11 C-labeled candidate. In this project, we aimed to further extend our efforts and develop an 18 F-labeled derivative, coined [ 18 F]ENL30. Fluorine-18 has several advantages over carbon-11 especially within the preclinical phase, where a long half-life usually increases evaluation throughput. ENL30 was successfully synthesized in a low albeit sufficient overall yield. Radiolabeling succeeded with a radiochemical yield of approximately 4.5%. Subsequent preclinical PET studies revealed that [ 18 F]ENL30 binds specifically to the 5-HT 7 R but suffered from affinity to σ-receptors. Additionally, we identified [ 18 F]ENL30 to be a P-gp substrate in rats. However, we believe that [ 18 F]ENL30 may prove to be valuable in higher species that exhibit decreased P-gp dependency. If required, σ-receptor binding could, in such studies, be selectively blocked potentially allowing for selective 5-HT 7 R imaging.
AB - The 5-HT 7 receptor (5-HT 7 R) is involved in a broad range of physiological conditions and disorders. Currently, there is no validated clinical positron emission tomography (PET) tracer available; however, we have recently developed a promising 11 C-labeled candidate. In this project, we aimed to further extend our efforts and develop an 18 F-labeled derivative, coined [ 18 F]ENL30. Fluorine-18 has several advantages over carbon-11 especially within the preclinical phase, where a long half-life usually increases evaluation throughput. ENL30 was successfully synthesized in a low albeit sufficient overall yield. Radiolabeling succeeded with a radiochemical yield of approximately 4.5%. Subsequent preclinical PET studies revealed that [ 18 F]ENL30 binds specifically to the 5-HT 7 R but suffered from affinity to σ-receptors. Additionally, we identified [ 18 F]ENL30 to be a P-gp substrate in rats. However, we believe that [ 18 F]ENL30 may prove to be valuable in higher species that exhibit decreased P-gp dependency. If required, σ-receptor binding could, in such studies, be selectively blocked potentially allowing for selective 5-HT 7 R imaging.
U2 - 10.1021/acsomega.9b00394
DO - 10.1021/acsomega.9b00394
M3 - Journal article
AN - SCOPUS:85064980018
SN - 2470-1343
VL - 4
SP - 7344
EP - 7353
JO - ACS Omega
JF - ACS Omega
IS - 4
ER -